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Khatamzas, Elham ORCID: 0000-0001-9253-1340; Antwerpen, Markus H. ORCID: 0000-0003-4013-8808; Rehn, Alexandra; Graf, Alexander; Hellmuth, Johannes Christian; Hollaus, Alexandra; Mohr, Anne-Wiebe; Gaitzsch, Erik; Weiglein, Tobias; Georgi, Enrico; Scherer, Clemens; Stecher, Stephanie-Susanne ORCID: 0000-0001-6715-1020; Gruetzner, Stefanie; Blum, Helmut; Krebs, Stefan; Reischer, Anna; Leutbecher, Alexandra; Subklewe, Marion; Dick, Andrea; Zange, Sabine; Girl, Philipp; Müller, Katharina; Weigert, Oliver; Hopfner, Karl-Peter ORCID: 0000-0002-4528-8357; Stemmler, Hans-Joachim; Bergwelt-Baildon, Michael von; Keppler, Oliver T. ORCID: 0000-0002-1384-8946; Wölfel, Roman; Muenchhoff, Maximilian; Moosmann, Andreas (2022): Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection. Nature Communications, 13: 5586. ISSN 2041-1723

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Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.

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